Camptothecin (Chem. Abstracts Registry No. 7689-03-4) is a naturally occurring compound found in Camptotheca acuminata (Nyssaceae) which has antileukemic and antitumor properties. Numerous camptothecin analogs having like properties are known, examples being those described in U.S. Pat. No. 4,894,456 to Wall et al. and European Patent Application No. 0 325 247 of Yaegashi et al.
A number of syntheses for camptothecin and camptothecin analogs are known. Most recently, parallel synthesis for camptothecin and camptothecin analogs have been disclosed in U.S. Pat. No. 5,162,532 to Comins and Baevsky. According to the methods disclosed therein, camptothecin and analogs thereof are prepared from the intermediates disclosed therein. One of the intermediates disclosed therein is the DE ring intermediate.
One method of synthesizing the DE ring intermediate was previously disclosed in Comins, D. L. The Synthesis of Analogs of Camptothecin, Ph.D. Thesis, University of New Hampshire, May 1977. A second method was disclosed in U.S. Pat. No. 5,162,532 to Comins and Baevsky. Subsequently, U.S. Pat. No. 5,212,3 17 to Comins and Baevsky, disclosed an alternate method of producing the DE ring intermediate.
An object of the present invention is to provide new methods for preparing DE ring intermediates, and novel intermediates useful for the preparation of such compounds, all of which are useful for the synthesis of camptothecin and camptothecin analogs.